tbuckley/cabot-search huggingface dataset:
Noncoding RNAs as regulators of STAT3 pathway in gastrointestinal cancers: Roles in cancer progression and therapeutic response
Authors: Milad Ashrafizadeh, Chakrabhavi D. Mohan, Shobith Rangappa, Ali Zarrabi, Kiavash Hushmandi, Alan Prem Kumar, Gautam Sethi, Kanchugarakoppal S. Rangappa
Journal: Medicinal Research Reviews (2023)

Abstract Gastrointestinal (GI) tumors (cancers of the esophagus, gastric, liver, pancreas, colon, and rectum) contribute to a large number of deaths worldwide. STAT3 is an oncogenic transcription factor that promotes the transcription of genes associated with proliferation, antiapoptosis, survival, and metastasis. STAT3 is overactivated in many human malignancies including GI tumors which accelerates tumor progression, metastasis, and drug resistance. Research in recent years demonstrated that noncoding RNAs (ncRNAs) play a major role in the regulation of many signaling pathways including the STAT3 pathway. The major types of endogenous ncRNAs that are being extensively studied in oncology are microRNAs, long noncoding RNAs, and circular RNAs. These ncRNAs can either be tumor‐promoters or tumor‐suppressors and each one of them imparts their activity via different mechanisms. The STAT3 pathway is also tightly modulated by ncRNAs. In this article, we have elaborated on the tumor‐promoting role of STAT3 signaling in GI tumors. Subsequently, we have comprehensively discussed the oncogenic as well as tumor suppressor functions and mechanism of action of ncRNAs that are known to modulate STAT3 signaling in GI cancers.
Use of baricitinib in treatment of COVID‐19: a systematic review
Authors: Ananyan Sampath, Aditya Banerjee, Shubham Atal, Ratinder Jhaj
Journal: Medicinal Research Reviews (2023)

Abstract Objective To assess the role of baricitinib alone or in combination with other therapies as a treatment for patients with COVID‐19. Methods Systematic literature search was conducted in the WHO COVID‐19 coronavirus disease database to find clinical studies on use of baricitinib for treatment of COVID‐19 between December 1, 2019 and September 30, 2021. Two independent set of reviewers identified the eligible studies fulfilling the inclusion criteria, relevant data was extracted and a qualitative synthesis of evidence performed. The risk of bias was evaluated with validated tools. Results A total of 267 articles were found to be eligible after primary screening of titles and abstracts. Following assessment of full texts, 19 studies were finally included for this systematic review, out of which 16 are observational, and 3 are interventional studies. Collating the results from these observational and interventional studies, baricitinib used as add‐on to standard therapy, either alone or in combination with other drugs, was found to have favorable outcomes in hospitalized patients with moderate to severe COVID‐19. Furthermore, ongoing trials indicate that the drug is being extensively studied across the world for its safety and efficacy in COVID‐19. Conclusion Baricitinib significantly improves clinical outcomes in hospitalized patients with COVID‐19 pneumonia, and further evidence will establish the drug as a standard treatment among such patients.
Monitoring the progress achieved towards ending tuberculosis in the European Union/European Economic Area, 2018 to 2021
Authors: Veronica Cristea, Csaba Ködmön, Senia Rosales-Klintz, Anastasia Pharris, Marieke J van der Werf
Journal: Eurosurveillance (2023)

We report progress in the European Union/European Economic Area (EU/EEA) towards the Sustainable Development Goal target for tuberculosis (TB) and for the associated global/regional targets. The TB notification rate and the number of TB deaths declined since 2015 but, if current trends continue, the EU/EEA will not reach the 2030 targets. Performance on treatment initiation targets declined sharply during 2020-2021, while the percentage of TB cases with successful treatment outcomes remains low, at 47.9% of the multidrug-resistant TB cases.
Adhesive cryogel particles for bridging confined and irregular tissue defects
Authors: Yao-Ting Xue, Ming-Yu Chen, Jia-Sheng Cao, Lei Wang, Jia-Hao Hu, Si-Yang Li, Ji-Liang Shen, Xin-Ge Li, Kai-Hang Zhang, Shu-Qiang Hao, Sarun Juengpanich, Si-Bo Cheng, Tuck-Whye Wong, Xu-Xu Yang, Tie-Feng Li, Xiu-Jun Cai, Wei Yang
Journal: Military Medical Research (2023)

Abstract Background Reconstruction of damaged tissues requires both surface hemostasis and tissue bridging. Tissues with damage resulting from physical trauma or surgical treatments may have arbitrary surface topographies, making tissue bridging challenging. Methods This study proposes a tissue adhesive in the form of adhesive cryogel particles (ACPs) made from chitosan, acrylic acid, 1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) and N-hydroxysuccinimide (NHS). The adhesion performance was examined by the 180-degree peel test to a collection of tissues including porcine heart, intestine, liver, muscle, and stomach. Cytotoxicity of ACPs was evaluated by cell proliferation of human normal liver cells (LO2) and human intestinal epithelial cells (Caco-2). The degree of inflammation and biodegradability were examined in dorsal subcutaneous rat models. The ability of ACPs to bridge irregular tissue defects was assessed using porcine heart, liver, and kidney as the ex vivo models. Furthermore, a model of repairing liver rupture in rats and an intestinal anastomosis in rabbits were established to verify the effectiveness, biocompatibility, and applicability in clinical surgery. Results ACPs are applicable to confined and irregular tissue defects, such as deep herringbone grooves in the parenchyma organs and annular sections in the cavernous organs. ACPs formed tough adhesion between tissues [(670.9 ± 50.1) J/m 2 for the heart, (607.6 ± 30.0) J/m 2 for the intestine, (473.7 ± 37.0) J/m 2 for the liver, (186.1 ± 13.3) J/m 2 for muscle, and (579.3 ± 32.3) J/m 2 for the stomach]. ACPs showed considerable cytocompatibility in vitro study, with a high level of cell viability for 3 d [(98.8 ± 1.2) % for LO2 and (98.3 ± 1.6) % for Caco-2]. It has comparable inflammation repair in a ruptured rat liver ( P = 0.58 compared with suture closure), the same with intestinal anastomosis in rabbits ( P = 0.40 compared with suture anastomosis). Additionally, ACPs-based intestinal anastomosis (less than 30 s) was remarkably faster than the conventional suturing process (more than 10 min). When ACPs degrade after surgery, the tissues heal across the adhesion interface. Conclusions ACPs are promising as the adhesive for clinical operations and battlefield rescue, with the capability to bridge irregular tissue defects rapidly.
Mental Distress Among Female Individuals of Reproductive Age and Reported Barriers to Legal Abortion Following the US Supreme Court Decision to Overturn <i>Roe v Wade</i>
Authors: Dhaval Dave, Wei Fu, Muzhe Yang
Journal: JAMA Network Open (2023)

This case-control study investigates the association of the US Supreme Court decision to overturn Roe v Wade with mental distress among female individuals of reproductive age.
VEGF-B hypertrophy predisposes to transition from diastolic to systolic heart failure in hypertensive rats
Authors: Anne-Maj Samuelsson, Theda Ulrike Patricia Bartolomaeus, Harithaa Anandakumar, Irene Thowsen, Elham Nikpey, Jianhua Han, Lajos Marko, Kenneth Finne, Olav Tenstad, Johannes Eckstein, Nikolaus Berndt, Titus Kühne, Sarah Kedziora, Ibrahim Sultan, Trude Skogstrand, Tine V Karlsen, Harri Nurmi, Sofia K Forslund, Entela Bollano, Kari Alitalo, Dominik N Muller, Helge Wiig
Journal: Cardiovascular Research (2023)

Abstract Aims Cardiac energy metabolism is centrally involved in heart failure (HF), although the direction of the metabolic alterations is complex and likely dependent on the particular stage of HF progression. Vascular endothelial growth factor B (VEGF-B) has been shown to modulate metabolic processes and to induce physiological cardiac hypertrophy; thus, it could be cardioprotective in the failing myocardium. This study investigates the role of VEGF-B in cardiac proteomic and metabolic adaptation in HF during aldosterone and high-salt hypertensive challenges. Methods and results Male rats overexpressing the cardiac-specific VEGF-B transgene (VEGF-B TG) were treated for 3 or 6 weeks with deoxycorticosterone-acetate combined with a high-salt (HS) diet (DOCA + HS) to induce hypertension and cardiac damage. Extensive longitudinal echocardiographic studies of HF progression were conducted, starting at baseline. Sham-treated rats served as controls. To evaluate the metabolic alterations associated with HF, cardiac proteomics by mass spectrometry was performed. Hypertrophic non-treated VEGF-B TG hearts demonstrated high oxygen and adenosine triphosphate (ATP) demand with early onset of diastolic dysfunction. Administration of DOCA + HS to VEGF-B TG rats for 6 weeks amplified the progression from cardiac hypertrophy to HF, with a drastic drop in heart ATP concentration. Dobutamine stress echocardiographic analyses uncovered a significantly impaired systolic reserve. Mechanistically, the hallmark of the failing TG heart was an abnormal energy metabolism with decreased mitochondrial ATP, preceding the attenuated cardiac performance and leading to systolic HF. Conclusions This study shows that the VEGF-B TG accelerates metabolic maladaptation which precedes structural cardiomyopathy in experimental hypertension and ultimately leads to systolic HF.
Durability of immune responses to mRNA booster vaccination against COVID-19
Authors: Prabhu S Arunachalam, Lilin Lai, Hady Samaha, Yupeng Feng, Mengyun Hu, Harold Sai-Yin Hui, Bushra Wali, Madison Ellis, Meredith E Davis-Gardner, Christopher Huerta, Kareem Bechnak, Sarah Bechnak, Matthew Lee, Matthew B Litvack, Cecilia Losada, Alba Grifoni, Alessandro Sette, Veronika I Zarnitsyna, Nadine Rouphael, Mehul S Suthar, Bali Pulendran
Journal: Journal of Clinical Investigation (2023)

BackgroundMaintaining durable immunity following vaccination represents a major challenge, but whether mRNA booster vaccination improves durability is unknown.MethodsWe measured antibody responses in 55 healthy adults, who received a booster dose of the Pfizer-BioNTech or Moderna vaccine against SARS-CoV-2 and calculated the half-life of the antibody titers. We also measured memory B and T cell responses in a subset of 28 participants. In 13 volunteers who received a second booster vaccine, we measured serum antibody titers and memory B and T cell responses.ResultsThe booster (third immunization) dose at 6 to 10 months increased the half-life of the serum-neutralizing antibody (nAb) titers to 76 days from 56 to 66 days after the primary 2-dose vaccination. A second booster dose (fourth immunization) a year after the primary vaccination further increased the half-life to 88 days. However, despite this modestly improved durability in nAb responses against the ancestral (WA.1) strain, there was a loss of neutralization capacity against the Omicron subvariants BA.2.75.2, BQ.1.1, and XBB.1.5 (48-, 71-, and 66-fold drop in titers, respectively, relative to the WA.1 strain). Although only 45% to 65% of participants demonstrated a detectable nAb titer against the newer variants after the booster (third dose), the response declined to below the detection limit in almost all individuals by 6 months. In contrast, booster vaccination induced antigen-specific memory B and T cells that persisted for at least 6 months.ConclusionThe durability of serum antibody responses improves only marginally following booster immunizations with the Pfizer-BioNTech or Moderna mRNA vaccines.
Reduced-Frequency Endocrine Therapy and Challenges of Noninferiority Study Designs
Authors: Carol J. Fabian, Dinesh Pal Mudaranthakam
Journal: JAMA Oncology (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
FLASH Radiotherapy in a Value-Based Health Care Environment
Authors: Dimitri Alex Dimitroyannis
Journal: JAMA Oncology (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
2022 American Thoracic Society BEAR Cage Winning Proposal: Passive Respiratory Exposure Detection—Investigation of COPD Triggers (PREDICT)
Authors: John C. Huston
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

"2022 American Thoracic Society BEAR Cage Winning Proposal: Passive Respiratory Exposure Detection - Investigation of COPD Triggers (PREDICT)." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp. –
First-in-human, phase 1 study of PF-06753512, a vaccine-based immunotherapy regimen (VBIR), in non-metastatic hormone-sensitive biochemical recurrence and metastatic castration-resistant prostate cancer (mCRPC)
Authors: Karen A Autio, Celestia S Higano, Luke Nordquist, Leonard J Appleman, Tian Zhang, Xin-Hua Zhu, Hani Babiker, Nicholas J Vogelzang, Sandip M Prasad, Michael T Schweizer, Ravi A Madan, Stephane Billotte, Nora Cavazos, Orlaith Bogg, Ray Li, Kam Chan, Helen Cho, Megan Kaneda, I-Ming Wang, Jenny Zheng, Szu-Yu Tang, Robert Hollingsworth, Kenneth A Kern, Daniel P Petrylak
Journal: Journal for ImmunoTherapy of Cancer (2023)

Background This phase 1 study evaluated PF-06753512, a vaccine-based immunotherapy regimen (PrCa VBIR), in two clinical states of prostate cancer (PC), metastatic castration-resistant PC (mCRPC) and biochemical recurrence (BCR). Methods For dose escalation, patients with mCRPC received intramuscular PrCa VBIR (adenovirus vector and plasmid DNA expressing prostate-specific membrane antigen (PSMA), prostate-specific antigen (PSA), and prostate stem cell antigen (PSCA)) with or without immune checkpoint inhibitors (ICIs, tremelimumab 40 or 80 mg with or without sasanlimab 130 or 300 mg, both subcutaneous). For dose expansion, patients with mCRPC received recommended phase 2 dose (RP2D) of PrCa VBIR plus tremelimumab 80 mg and sasanlimab 300 mg; patients with BCR received PrCa VBIR plus tremelimumab 80 mg (Cohort 1B-BCR) or tremelimumab 80 mg plus sasanlimab 130 mg (Cohort 5B-BCR) without androgen deprivation therapy (ADT). The primary endpoint was safety. Results Ninety-one patients were treated in dose escalation (mCRPC=38) and expansion (BCR=35, mCRPC=18). Overall, treatment-related and immune-related adverse events occurred in 64 (70.3%) and 39 (42.9%) patients, with fatigue (40.7%), influenza-like illness (30.8%), diarrhea (23.1%), and immune-related thyroid dysfunction (19.8%) and rash (15.4%), as the most common. In patients with mCRPC, the objective response rate (ORR, 95% CI) was 5.6% (1.2% to 15.4%) and the median radiographic progression-free survival (rPFS) was 5.6 (3.5 to not estimable) months for all; the ORR was 16.7% (3.6% to 41.4%) and 6-month rPFS rate was 45.5% (24.9% to 64.1%) for those who received RP2D with measurable disease (n=18). 7.4% of patients with mCRPC achieved a ≥50% decline in baseline PSA (PSA-50), with a median duration of 4.6 (1.2–45.2) months. In patients with BCR, 9 (25.7%) achieved PSA-50; the median duration of PSA response was 3.9 (1.9–4.2) and 10.1 (6.9–28.8) months for Cohorts 5B-BCR and 1B-BCR. Overall, antigen specific T-cell response was 88.0% to PSMA, 84.0% to PSA, and 80.0% to PSCA. Conclusions PrCa VBIR overall demonstrated safety signals similar to other ICI combination trials; significant side effects were seen in some patients with BCR. It stimulated antigen-specific immunity across all cohorts and resulted in modest antitumor activity in patients with BCR without using ADT. Trial registration number NCT02616185 .
Intrathecal AAV9/AP4M1 gene therapy for hereditary spastic paraplegia 50 shows safety and efficacy in preclinical studies
Authors: Xin Chen, Thomas Dong, Yuhui Hu, Raffaella De Pace, Rafael Mattera, Kathrin Eberhardt, Marvin Ziegler, Terry Pirovolakis, Mustafa Sahin, Juan S. Bonifacino, Darius Ebrahimi-Fakhari, Steven J. Gray
Journal: Journal of Clinical Investigation (2023)

Spastic paraplegia 50 (SPG50) is an ultrarare childhood-onset neurological disorder caused by biallelic loss-of-function variants in the AP4M1 gene. SPG50 is characterized by progressive spastic paraplegia, global developmental delay, and subsequent intellectual disability, secondary microcephaly, and epilepsy. We preformed preclinical studies evaluating an adeno-associated virus (AAV)/AP4M1 gene therapy for SPG50 and describe in vitro studies that demonstrate transduction of patient-derived fibroblasts with AAV2/AP4M1, resulting in phenotypic rescue. To evaluate efficacy in vivo, Ap4m1-KO mice were intrathecally (i.t.) injected with 5 × 1011, 2.5 × 1011, or 1.25 × 1011 vector genome (vg) doses of AAV9/AP4M1 at P7-P10 or P90. Age- and dose-dependent effects were observed, with early intervention and higher doses achieving the best therapeutic benefits. In parallel, three toxicology studies in WT mice, rats, and nonhuman primates (NHPs) demonstrated that AAV9/AP4M1 had an acceptable safety profile up to a target human dose of 1 × 1015 vg. Of note, similar degrees of minimal-to-mild dorsal root ganglia (DRG) toxicity were observed in both rats and NHPs, supporting the use of rats to monitor DRG toxicity in future i.t. AAV studies. These preclinical results identify an acceptably safe and efficacious dose of i.t.-administered AAV9/AP4M1, supporting an investigational gene transfer clinical trial to treat SPG50.
Subcutaneous vs Intravenous Administration of Medications and Fluids for Patients With Cancer in the US and Canada
Authors: Michael Tang, Mohamed Abdelaal, Jenny Lau, Alejandra Ruiz Buenrostro, Minxing Chen, Camilla Zimmermann, Eduardo Bruera
Journal: JAMA Oncology (2023)

This cross-sectional study compares rates of subcutaneous and intravenous administration of medications and fluids among patients with cancer in 2 acute palliative care units in the US and Canada.
Stop or Not: Genome-Wide Profiling of Reassigned Stop Codons in Ciliates
Authors: Wenbing Chen, Yupeng Geng, Bing Zhang, Ying Yan, Fangqing Zhao, Miao Miao
Journal: Molecular Biology and Evolution (2023)

Bifunctional stop codons that have both translation and termination functions in the same species are important for understanding the evolution and function of genetic codes in living organisms. Considering the high frequency of bifunctional codons but limited number of available genomes in ciliates, we de novo sequenced seven representative ciliate genomes to explore the evolutionary history of stop codons. We further propose a stop codon reassignment quantification method (stopCR) that can identify bifunctional codons and measure their frequencies in various eukaryotic organisms. Using our newly developed method, we found two previously undescribed genetic codes, illustrating the prevalence of bifunctional stop codons in ciliates. Overall, evolutionary genomic analyses suggest that gain or loss of reassigned stop codons in ciliates is shaped by their living environment, the eukaryotic release factor 1, and suppressor tRNAs. This study provides novel clues about the functional diversity and evolutionary history of stop codons in eukaryotic organisms.
STING agonist-loaded mesoporous manganese-silica nanoparticles for vaccine applications
Authors: Cheng Xu, Hannah E. Dobson, Mengjie Yu, Wang Gong, Xiaoqi Sun, Kyung Soo Park, Andrew Kennedy, Xingwu Zhou, Jin Xu, Yao Xu, Andrew W. Tai, Yu Leo Lei, James J. Moon
Journal: Journal of Controlled Release (2023)
Sphingolipid desaturase DEGS1 is essential for mitochondria-associated membrane integrity
Authors: Laura Planas-Serra, Nathalie Launay, Leire Goicoechea, Bénédicte Heron, Cristina Jou, Natalia Juliá-Palacios, Montserrat Ruiz, Stéphane Fourcade, Carlos Casasnovas, Carolina De La Torre, Antoinette Gelot, Maria Marsal, Pablo Loza-Alvarez, Àngels García-Cazorla, Ali Fatemi, Isidre Ferrer, Manel Portero-Otin, Estela Area-Gómez, Aurora Pujol
Journal: Journal of Clinical Investigation (2023)

Sphingolipids function as membrane constituents and signaling molecules, with crucial roles in human diseases, from neurodevelopmental disorders to cancer, best exemplified in the inborn errors of sphingolipid metabolism in lysosomes. The dihydroceramide desaturase Δ4-dihydroceramide desaturase 1 (DEGS1) acts in the last step of a sector of the sphingolipid pathway, de novo ceramide biosynthesis. Defects in DEGS1 cause the recently described hypomyelinating leukodystrophy-18 (HLD18) (OMIM #618404). Here, we reveal that DEGS1 is a mitochondria-associated endoplasmic reticulum membrane-resident (MAM-resident) enzyme, refining previous reports locating DEGS1 at the endoplasmic reticulum only. Using patient fibroblasts, multiomics, and enzymatic assays, we show that DEGS1 deficiency disrupts the main core functions of the MAM: (a) mitochondrial dynamics, with a hyperfused mitochondrial network associated with decreased activation of dynamin-related protein 1; (b) cholesterol metabolism, with impaired sterol O-acyltransferase activity and decreased cholesteryl esters; (c) phospholipid metabolism, with increased phosphatidic acid and phosphatidylserine and decreased phosphatidylethanolamine; and (d) biogenesis of lipid droplets, with increased size and numbers. Moreover, we detected increased mitochondrial superoxide species production in fibroblasts and mitochondrial respiration impairment in patient muscle biopsy tissues. Our findings shed light on the pathophysiology of HLD18 and broaden our understanding of the role of sphingolipid metabolism in MAM function.